Dose escalation, placebo-controlled phase 1 study to assess the safety and tolerability of CSL324 in healthy adults
A single dose ascending and repeated dose, randomised, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy, adult male and female subjects.
CSL Limited
58 participants
Jun 30, 2016
Interventional
Conditions
Summary
This is a first-in-human, randomised, double-blind, placebo-controlled study. The study is designed to assess the safety, tolerability and pharmacokinetics of single ascending dose (Parts A and B) and repeated (Part C) intravenous infusions of CSL324 or placebo (saline) in healthy subjects. Subjects will have blood collected at various time points for safety laboratory evaluations, absolute neutrophil count (ANC) and pharmacokinetic (PK) and pharmacodynamic (PD) sampling, and will be assessed for 3 months after infusion to assess immunogenicity and longer term safety. Skin test(s) will be used to assess the anti-inflammatory effect of CSL324 in response to an inflammatory stimulus (Parts A and B). Cerebrospinal fluid will be collected by lumbar puncture from subjects in the highest dose group in Part A after the last infusion of CSL324 or placebo, to determine whether CSL324 distributes into the cerebrospinal fluid. Subjects in Part B will also receive multiple subcutaneous doses of filgrastim to stimulate an increase in circulating neutrophils and provide additional PD data.
Eligibility
Inclusion Criteria4
- Healthy, male or female, 18 to 55 years of age
- Body mass index range of 18.5 to 32.0 kg/m^2, inclusive, and weight at least 50 kg and less than 100 kg
- Females must be of non-childbearing potential
- Male subject and their female spouse/partners who are of childbearing potential must be using 2 forms of highly effective birth control
Exclusion Criteria4
- History or evidence of any clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy
- History of venous thrombosis, polycythaemia or thrombophilia
- History of autoimmune disease with the exception of seasonal allergic rhinitis managed without systemic glucocorticoid treatment
- Any history of cyclic neutropenia or a Screening absolute neutrophil count < 2.0 × 10^9/L
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Interventions
The study will consist of 3 parts (Parts A, B and C). Subjects can participate in only 1 part and in only 1 dose group; in each part, subjects will be randomly assigned to either CSL324 or placebo. In Parts A and B a single infusion of either CSL324 or placebo will be administered; dose escalation may occur in these parts. There may be up to 6 subjects per dose in Parts A and B. In Part C, 10 subjects will receive 3 infusions at 21 day intervals of either CSL324 or placebo (according to their randomisation and at the same dose per infusion). Intervention 1: Single (Parts A and B) or repeat (Part C) dose(s) of anti-human granulocyte-colony stimulating factor (G-CSF) receptor monoclonal antibody (CSL324) will be administered intravenously. The dose and infusion volume will be based upon the subject's body weight and the allowable drug concentration. Dose escalation requires Safety Review Committee review (of available blinded safety, tolerability, PK and selected PD data) and approval. In addition to CSL324 or placebo, subjects may also receive other interventions (G-CSF and/or Cantharidin) as described below. Intervention 2: Filgrastim (Registered Trademark: Neupogen), a recombinant form of human G-CSF, will be administered subcutaneously once a day, at approximately the same time each day on up to 6 consecutive days (from 3 days before and/or up to 3 days after CSL324 or placebo infusion depending upon the CSL324 or placebo dose amount) at a dose based upon the subject's body weight (5 microgram/kg; all Part B subjects only) Intervention 3: Cantharidin (Registered Trademark: Cantharone), will be applied topically to the skin (on the arm), to induce a blister (all Parts A and B subjects only). Cantharidin (25 microlitres at 0.1 % weight/volume) will be administered once a day, on 2 separate days, 2 or 3 days apart (from 1 day before and up to 2 days after CSL324 or placebo infusion depending upon the CSL324 or placebo dose amount).
Locations(1)
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ACTRN12616000846426